The present invention relates to electrotherapy, and provides apparatus and methods for application of such therapy.
There are a number of electrotherapy techniques that induce action potentials. Aβ fibres have low thresholds that enable them to respond to such innocuous events as movement, vibration and light touch. Melzack and Wall 1965 and Wall 1986 described how analgesia could be produced when Aβ fibres are stimulated at 100 Hz, a frequency that none of the other sensory nerves can follow faithfully. Wall 1986 produced these effects by applying the current through needles inserted into the patient's nerves. To avoid the inconvenience and possible complications of inserting needles into nerves, he soon employed surface electrodes, leading to the term Transcutaneous Electrical Nerve Stimulation (TENS).
Woolf 1989 reviewed the use of these devices, and described their electrical parameters. The usual TENS machine develops a pulse, whose width can be varied from 50-500 μs, employing a current whose amplitude can be increased from 0-50 mA, and whose frequency is generally 100 Hz. The TENS pulse width (50-500 μs) is sufficiently long in duration to excite Aβ nerves at low voltage causing a painless tingling and stimulation of interneurones releasing GABA (Duggan et al 1985) that inhibits the release of SP within the spinal cord by C-fibres. Johnson et al 1991 showed that ‘high intensity stimulation’; where the amplitude is increased sufficiently to recruit Aδ fibres, invokes release of met-enkephalin in the spinal cord which produces a more prolonged analgesic effect than that provided by the release of GABA produced by the more usual ‘low intensity stimulation’ of Aβ fibres. Salar et al 1981 observed opioids were released slowly into the cerebrospinal fluid when TENS is performed at frequencies of 40-60 Hz and at amplitudes of 40-80 mA: signals that readily recruit Aδ fibres, whose firing is associated with sharp pain.
To stimulate Aβ fibres, frequencies below 1 kHz are employed. The typical TENS device runs at 100 Hz. However the TENS frequency may be reduced still further to below 80 Hz.
As tissue impedance is capacitive, it tends to fall as frequency is increased. In order to increase tissue penetration, signals may be provided at a frequency where the intervals between each electric signal are less than the refractory periods of axons that require stimulation. In order to produce action potentials, such signals are modulated to provide low frequency stimulation either by interference or interruption.
The interference method of applying medium frequency currents is exemplified by Nemec U.S. Pat. No. 2,622,601, Griffith U.S. Pat. No. 3,096,768 and many others. Two signal sources are each connected to a pair of electrodes. They can produce an amplitude modulated medium frequency signal in the tissues called interferential current as follows. The first signal source uses a medium frequency carrier wave (typically 4.0 kHz) while the other operates at a slightly different frequency (typically 4.1 kHz). Their respective pairs of surface electrodes are arranged on the body in a manner that allows the two oscillating currents to meet in deep tissues where modulation produces interference or a beat frequency in the low frequency range typically at 100 Hz. This in turn is said to stimulate deeply placed Aβ fibres to produce analgesia.
As an example of the interrupted form of modulation, in order to avoid the surgical complications of implanting electrodes in direct contact with the brain, Limoge U.S. Pat. No. 3,835,833 and Stinus et al 1990 describe Transcutaneous Cranial Stimulation (TCES), an application of intermittent 4 ms trains of medium frequency current (typically 166 kHz) arranged so each pulse provided is 100 mA peak-to peak to a patient's head via one frontal cathode and two posterior anodes (one placed over each mastoid process). The positive going element of each pulse (67 mA) lasts 2 μs; while the negative going portion has a lower amplitude of 33 mA but lasts 4 μs. Each 4 ms train is repeated typically at 77 or 100 times per second. The medium frequency is employed to penetrate the tissues of the brain from surface electrodes. Stinus (1990) has observed that such stimulation only raised pain thresholds when opiates have been administered.
Macdonald and Coates GB 2290033, U.S. Pat. No. 5,776,170 explored the effects of applying signals whose pulse width is so brief, typically 4 μs, that the voltage gated channels lying in excitable membranes of peripheral nerve axons that lie in the path of the current do not have time to respond to these electric signals sufficiently to reach membrane threshold and produce action potentials. This form of electrotherapy produces analgesic and mood altering effects provided that surface electrodes are placed over the spinal cord. Macdonald and Coates 1995 called this method TSE (Transcutaneous Spinal Electroanalgesia). Towell et al 1997 performed a controlled trial that demonstrated TSE produces beneficial changes in mood provided the electrodes are placed over the spinal cord.
GB2290033 states that as frequency is increased the voltage has to be reduced. The document quotes 150V as being a sufficient voltage at 5 kHz and 25V as being sufficient at 150 kHz.
The present invention provides methods and apparatus related to electrotherapy, which address certain limitations or disadvantages of the prior art.
In a first aspect, the present invention provides an apparatus for producing analgesia in a patient through electrical signals applied by electrodes to the patient's body, the apparatus comprising electrodes for application to the patient's body and a signal generator which is connectable to the electrodes, wherein the signal generator is arranged to generate a biphasic waveform comprising successive cycles each containing a positive and negative pulse, wherein the mean pulse width Pw is less than 10 μs, and wherein Vp2·Pw·Fp is at least 200, where Vp is the mean pulse voltage, and Fp is the number of forward and reverse pulses per second.
In this application, references to waveform are to an electrical waveform. The term “pulse” refers to either the positive or negative (forward or reverse) element of the biphasic waveform. Hence the pulse voltage is the amplitude (V) of the positive or negative pulse and the pulse frequency is the number of forward and reverse pulses per second, counting both. The pulse width Pw is measured in seconds.
A cycle consists of both a forward and reverse pulse. Therefore, the number of forward and reverse pulses per second (the pulse frequency) will be equal to twice the cycle frequency. The leading edge of the cycle can be either positive or negative. Normally, the leading pulse in each cycle will be of the same polarity, but this is not essential.
It has been found that the apparatus as described above can be used to deliver a high power treatment to a patient. This may be done without generating action potentials in sensory nerves at a level that might be uncomfortable (as would be the case for example with a TENS pulse).
It has also been found that embodiments of the present invention are capable of treating surprisingly large volumes of tissue, and/or treating deep structures more effectively than the prior art. Moreover, unlike conventional TSE treatment, it has been found that treatment is possible by applying the electrodes to the body at points which provide current flow in the region of the affected area, and not necessarily over the central nervous system. Among other things, this has been found to be helpful in reducing inflammation, which can for example be used to treat inflammatory arthritic and visceral disease.
The present waveform is referred to herein as a “HPSP” (high power short pulse) waveform. The relationship Vp2·Pw·Fp>=200 is derived from consideration of the power which can be applied to the patient. The mean power dissipation can be approximated to Wm=Pw·Fp·Vp2/Z where Wm is the mean power dissipation and Z is the impedance of the tissues and connecting means to the device (electrodes and leads). This aspect of the invention provides a greater power level for a given load impedance than was employed or suggested in the prior art. For example, at with signals applied that contain most energy in harmonics at frequencies of at least 20 kHz, the load impedance of the human body can be approximated at a constant 150Ω. Based on this, the maximum power taught by GB2290033 is 1.125 W. The present invention operates significantly above this level.
The relationship Vp2·Pw·Fp>=200 is equivalent to and can also be expressed as VRMS>=√200.
The high RMS value of the applied voltage when compared with other electrotherapy techniques produces similarly high RMS currents in the patient. For example, at VRMS=√200, the RMS current with a 150 Ωload (typical of a patient) would be 94 mA, which is six times higher than what is generally accepted to be a strong TENS signal of 15 mA.
Vp2·Pw·Fp may be at least 220, preferably it is at least 250, 340 or 500.
Due to heating effects at higher powers, it may be preferred that Vp2·Pw·Fp is below 1800, more preferably below 1200.
Preferably, the biphasic waveform is continuous. By a “continuous” biphasic waveform is meant a series of cycles in which the leading pulses are equally spaced.
The mean pulse width for the forward and reverse pulses, and preferably the pulse width of each of the forward and reverse pulses, may be 6 μs or less, 4 μs or less, e.g., 3 μs, 2 μs, 1.5 μs, 1 μs, 0.75 μs or less, and optionally at least 0.01 μs, 0.05 μs, or 0.5 μs. In some embodiments, short pulse widths are preferred so as to increase the rate of change of the electrical field, e.g., for a given mean modulus or RMS current in the tissues.
Without wishing to be bound by theory, the inventors believe increasing the rate of change of the electrical field may increase coupling to cellular structures involved in transmission of pain. The signal penetrates deep tissues, and it is believed that it may produce beneficial effects by producing changes that affect one or more processes that occur in the central and or peripheral nervous systems, for example the behaviour of microtubules, the rate of release of certain ligands and or the responses to them by various ligand gated receptors. The signal may also have effects on the mobility of ions associated with the transmission of action potentials and act directly on other cell structures such as voltage gated channels in both the peripheral and central nervous system.
In some embodiments of the invention, it is preferred that the mean pulse voltage, and preferably the voltage of each positive and negative pulse, is at least 100V, preferably 150V and more preferably 200V. Optionally, the mean pulse voltage and/or voltage of each pulse has an upper limit of 500V, 400V, 300V or 250V, e.g., to meet safety requirements.
While all combinations of preferred voltages and pulse widths are specifically included, optionally, when the voltage (mean value or voltage of each pulse) is at least 100V, the pulse width (mean value or width of each pulse) is 6 μs or 4 μs or less; when the voltage is at least 150V the pulse width is 3 μs or less; and when the voltage is at least 200V the pulse width is 1.5 μs or less.
The pulse frequency (i.e. the number of forward and reverse pulses per second) may be at least 1000 Hz or 1200 Hz, more preferably at least 5 KHz, and still more preferably 10 KHz, 20 KHz or above.
The pulse frequency may be less than 2 MHz, more preferably less than 1 MHz or 500 kHz, still more preferably less than 250 kHz or 100 kHz.
It is preferred that the duty cycle (the ratio of “on time” to “off time”) through one complete cycle should be less than 10% or 5%, preferably less than 2% or 1%, and greater than 0.1%, particularly where the biphasic wave is continuous.
Each pulse in the biphasic wave preferably has a rapid rise and fall phase, e.g., is substantially rectangular, subject to capacitor droop. Preferably the edge rate exceeds 250V4 μs, more preferably 500V/μs or 1000V/p.
Preferred embodiments of invention have a high pulse current during the pulse “on” time. For example the waveform may have a pulse current of at least 0.3 A throughout the pulse period. The current may vary over the pulse period due to capacitor droop, and may for example be 0.7 A-3 A at the start of the pulse, falling to 0.5 A to 2 A at the end of the pulse. The mean modulus current flowing through the patient is preferably at least 3 mA, preferably at least 6 mA and more preferably at least 10 mA. When measured at 150 ohm load, VRMS=√200 gives an RMS current of 94 mA.
The present inventors have found that sensation can be obtained with the wave form used in embodiments of the present invention. The inventors measured the threshold of sensation produced by a biphasic square wave, that is, the point at which sensation is first felt. While the voltage threshold of sensation was affected by the pulse width, it was substantially unaffected by the frequency. Unexpectedly, therefore the threshold of sensation is not affected by the RMS or mean modulus current. Moreover, sensation can be provided at pulse frequencies well above the physiological limits, those frequencies greater than that which Aβ fibres can faithfully follow, for example 800 Hz to 1200 Hz.
It has furthermore been found that the threshold of sensation can be varied by varying the interpulse spacing. As the interpulse spacing is reduced, the voltage at which sensation is first perceived for a given pulse width increases, particularly for pulse widths below 4 μs. This allows the level of sensation to be varied independently of the power level or current supplied by the device or the associated rate of change of the electrical field in the tissues. In some embodiments it may be desirable to reduce the level of sensation that is felt, so that there is low or no sensation, e.g., allowing the patient to sleep when the device is operating. Alternatively, it may be desirable to provide a mild sensation, as this can be comforting to the user, and can help to distract from aches and pains. It is also believed that some mild tingling might play a role in expression of neurotransmitters.
It may be preferred that the mean pulse width, and more preferably the pulse width of each forward and reverse pulse, is less than 4 μs, to improve the ability of the sensation level to be varied with the interpulse spacing.
The interpulse spacing may be less than 4 μs, preferably less than 3, 2 or 1 μs and most preferably 0 μs. In some embodiments, a low interpulse spacing may be used together with a low pulse width (mean value or value per pulse), e.g., a pulse width of 2 μs or less, more preferably a pulse width of 1.5 μs or 1 μs or less, to provide mild or no sensation even at high voltages (i.e., peak pulse voltages), such as greater than 150V, 200V or 250V. Without wishing to be bound by theory, it is believed that a low interpulse space and preferably an interpulse space of 0 μs may also be beneficial because it provides a high rate of change in the electrical field per pulse.
In other embodiments, e.g., where some sensation may be desirable, the interpulse spacing may be at least 5 μs, preferably at least 6, 7, 8, 9 or 10 μs.
The interpulse spacing may also be varied to alter the wave harmonics. Without wishing to be bound by theory, the present inventors believe that the harmonic content of the wave is important in determining its treatment efficacy. For instance, the continuous wave form which is preferred in this aspect of the invention produces a series of harmonics at frequencies spread widely over the spectrum, when compared to a burst wave form in which most of the wave energy is concentrated around a narrow peak.
The inventors have compared the harmonic components of a square wave of 2 μS pulse width with equal positive and negative pulses and zero inter pulse space, with a square wave of the same pulse width with 2 μS inter pulse space, both at a cycle frequency of 20 kHz. The spacing between components in both cases was 20 kHz, but the waveform with 2 μS inter pulse space has its peak at approximately half the frequency of the waveform with zero space.
The inventors also examined a square wave of 2 μS pulse width with cycle frequency of 5 kHz and inter pulse spacing of 100 μS; in this case the return pulses are equally spaced between the forward pulses. This provides an interesting result with two distinct curves made up of harmonic components of the signal. One could be said to represent the harmonic components of the cycle frequency and the other the components of the pulses themselves. This dual curve structure may be desirable in increasing the chance of exciting resonance in the cellular structures, regardless of natural variation between them, e.g., in orientation. Hence, in some embodiments, it may be desirable for the interpulse spacing to be at least 20, 40, 60, 80 or 100 μs, up to half the distance between cycles.
Preferred HPSP pulses range from 4 μS width with the main harmonic components of this centred around approximately 125 kHz, through to 0.05 μS or less, equivalent to 10 MHz, and incorporate pulse frequencies varying in the range 1200 Hz through to 2 MHz.
Selection of inter pulse space and pulse width therefore plays a primary role in determining the range of frequencies provided by the therapy.
HPSP therapy can be considered to be a form of radio frequency stimulation of the tissues with a much wider spread of harmonics than that associated with the known types of pulsed and continuous radio frequency electrotherapy in use today. The waveform parameters can be selected to deliver oscillating electric fields in the ranges of 1 kHz to 20 MHz or more. The region covering 50 kHz to 1 MHz (harmonics in fields) is thought to be that at which effects on cell structures and ion mobility are maximised and therefore this is the preferred range of frequencies that are employed.
Kotnik et al 2000 explored the degree of amplification of an external electric within the cell at various harmonic frequencies and showed the cell membrane amplifies externally applied alternating current electric fields by a factor of several thousands provided the harmonic frequency is 100 kHz or less. As harmonic frequency is increased above 100 kHz, this amplified effect greatly decreases, and the capacitive properties of structures contained within the cell and extracellular fluid become increasingly important. Liu et al 1990, studied the effects of oscillating electric fields on the activation of Na+ and K+ pumping modes of (Na,K)-ATPase. This is an active transport system (energised by the hydrolysis of ATP) in the membrane for regulating the extrusion of Na+ and influx of K+ ions into the cell (the sodium pump) either to maintain cellular electrolyte balance or provide action potential transmission. At a voltage of 20V/cm, various frequencies were tested and uncoupled transport modes were shown at two frequencies; increased influx only was observed at 1 kHz; while increased efflux only was observed at higher frequencies particularly 1 MHz.
In another aspect, the apparatus as described above can be used in a method of inducing analgesia in a patient, the method comprising applying the electrodes to the patient's body, and providing a waveform as described.
In another aspect of the invention, there is provided an apparatus for producing analgesia in a patient through electrical signals applied by electrodes to the patient's body, the apparatus comprising electrodes for application to the patient's body and a signal generator which is connectable to the electrodes, wherein the signal generator is arranged to generate a biphasic waveform comprising successive cycles each containing a positive and negative pulse, and wherein the apparatus comprises a control element for varying the spacing between the positive and negative pulse.
The mean pulse width, and preferably the width of each positive and negative pulse of the biphasic waveform, is preferably less than 4 μs, to maximise the ability to vary sensation by varying the interpulse spacing, and optionally at least 0.5 μs or 2 μs. Preferably, the control element for varying the spacing between the positive and negative pulse is able to vary the interpulse spacing between 0 μs and half of the cycle time, more preferably 0 μs and 20 μs or 0 μs and 10 μs.
This apparatus may be particularly beneficial at high mean pulse voltages, e.g., at least 100V, 150V or 200V where sensation is more likely to be experienced. More preferably, these voltages refer to the voltage of each pulse. Optionally, Vp2·Pw·Fp is at least 200 and/or less than 1200 or 1800. It may also or alternatively be preferred that pulse frequency is at least 1000 Hz or 1200 Hz, more preferably at least 5 kHz, and still more preferably 10 KHz, 20 KHz or above. The pulse frequency may be less than 2 MHz, more preferably less than 1 MHz or 500 kHz, still more preferably less than 250 kHz or 100 kHz. In some embodiments, the wave form may be a HPSP waveform, as above.
The control element may be operable by an operator, e.g., the user, for example so that the user can set the interpulse spacing to a level which provides a comfortable level of sensation.
Alternatively, the control element may provide automated variation of interpulse spacing, for example rhythmical modulation, or automated random modulation, e.g., in a series of modulation cycles. This may be of particular benefit at modulation rates below 1200 Hz, preferably modulation rates below 100 Hz or 50 Hz, and/or greater than 0.25 Hz, so as to modulate the sensory nerves within the physiological range. Moreover, since the carrier signal can be applied at well above the physiological range and with high peak voltages it may be of particular benefit when the power levels are fairly high so as to penetrate large volumes of tissues.
The control element may be for example a suitably programmed processor, a manual control or circuit adapted to provide a rhythmic or automated random modulation.
In some embodiments, the apparatus (preferably an apparatus having automated variation in the interpulse spacing) also comprises a control for varying the pulse voltage or pulse width or both, for example a control which would allow the base level of sensation to be set by the user.
In another aspect, the present invention provides a method of inducing analgesia through electrical signals applied by electrodes to the patient's body, wherein the induction of analgesia comprises
providing an apparatus comprising electrodes for application to the patient's body and a signal generator connected to said electrodes, wherein the signal generator is arranged to provide a biphasic electrical waveform comprising successive cycles each having a positive and negative pulse,applying the electrodes to two or more locations on the patient's body;
and providing said biphasic electrical waveform;
and wherein the spacing between the positive and negative pulse is modulated during the treatment.
The spacing between the positive and negative pulse can be modulated so as to alter the level of sensation experienced by the patient during the treatment.
In some embodiments, it may be preferred that the method comprises adjusting the interpulse spacing such that no sensation is felt, except optionally for a transient sensation which quickly fades. In other embodiments, it may be preferred that the interpulse spacing is adjusted to provide the user with mild sensation. For example, this can be reassuring to the user.
The modulation may take place one or more times during the treatment to achieve a desired sensation level, or may be ongoing or repeated, e.g., in a series of modulation cycles.
The modulation of interpulse spacing may also have beneficial treatment effects, for example, it may aid the expression of neurotransmitters or aid relaxation.
In preferred embodiments, the modulation is repeated during the treatment, e.g., randomly or rhythmically. The modulation rate of the interpulse spacing may preferably be below 1200 Hz, more preferably below 100 Hz or 50 Hz, and/or greater than 0.25 Hz, so as to modulate the sensory nerves within the physiological range. Preferably, the user experiences at least some sensation.
This method preferably allows use of a high voltage, high current signal which may penetrate deep tissues more effectively than a typical TENS pulse and then modulating the signal by varying the inter pulse spacing in such a way that action potentials are generated in deep nerves at interpulse spacing modulation rates well within the physiological range, preferably 0.25 Hz to 0.5 Hz to 50 Hz or 120 Hz.
In each of the above methods, the spacing can be modulated automatically, e.g., rhythmically (i.e. with an identifiable pattern even a complex one) or randomly, e.g., under control of a microprocessor, or via a manual control. When the method provides a particular, desired level of sensation, it may be preferred that the spacing is modulated by a manual control and/or a control which is operable by a user. In other embodiments, an automated control may be preferred. A random modulation may help in reducing adaption to the signal.
Each of the above methods may also comprise selecting the base level of sensation by adjusting the voltage or pulse width or both. For example, the base level may be selected such that the user experiences a transient sensation, e.g., at an interpulse spacing of 0 μs. Optionally, in setting the base level of sensation, the pulse width may be varied, and the pulse voltage maintained at a value of greater than 150, 180V or 200V. Modulation of the interpulse spacing may then give a good correlation between sensation and interpulse space.
In another aspect, the present invention provides a method for pre-setting the operating parameters of an apparatus for producing analgesia in a patient through electrical signals applied by electrodes to the patient's body, the apparatus comprising electrodes for application to the patient's body and a signal generator which is connectable to said electrodes, wherein the signal generator is arranged to provide a biphasic waveform comprising successive cycles each having a positive and negative pulse, the method comprising
selecting the voltage and pulse width, and
selecting the interpulse spacing with reference to a predetermined relationship between sensation and interpulse spacing at said voltage and pulse width.
In each of the above methods, preferred operating conditions and parameters of the waveform are as described for the above apparatus, comprising a control element for varying the spacing between the positive and negative pulse.
In another aspect, the present invention provides an apparatus for producing analgesia in a patient through electrical signals applied by electrodes to the patient's body, the apparatus comprising electrodes for application to the patient's body and a signal generator which is connectable to said electrodes, wherein the signal generator is arranged to provide a biphasic waveform comprising successive cycles each containing a positive and negative pulse, wherein the mean pulse width Pw is less than 1.5 μs and the spacing between the positive and negative pulse is between 0 μs and 2 μs.
Preferably, the mean pulse voltage (more preferably the voltage of each pulse) is at least 130V, more preferably at least 150V or 170V.
It may be preferred that the interpulse spacing is 1.5 μs or less, in which case the voltage (mean or voltage of each positive and negative pulse) may be at least 140V, preferably at least 160V or 180V. Still more preferably, the interpulse spacing may be 1 μs or less, in which case the voltage may be at least 180V, preferably at least 200V, more preferably at least 220V. An interpulse spacing of 0.5 μs or less, or 0 μs may be preferred in some embodiments. For example, a zero interpulse spacing may be advantageous in providing a high rate of change of the electrical field per pulse.
Preferably, the mean pulse width and preferably the width each pulse is less than 1.5 μs, more preferably less than 1.25, 1 μs or 0.75 μs.
In some embodiments, the pulse frequency may be at least 1000 or 1200 Hz, more preferably at least 5 kHz, 10 kHz or 20 kHz, and/or less that 2 MHz, 1 MHz, 500 kHz or 250 kHz. Optionally, Vp2·Pw·Fp is at least 200 and/or less than 1200 or 1800.
In another aspect the present invention provides a method of inducing analgesia in a patient's body through electrical signals applied by electrodes to the patient's body, using an apparatus comprising electrodes for application to the patient's body and a signal generator which is connectable to said electrodes, wherein the signal generator is arranged to generate a biphasic waveform comprising successive cycles each containing a positive and negative pulse, the method comprising:
applying the electrodes to two or more locations on the patient's body such that at least one of said locations on the patient's body does not overlie the central nervous system;
providing said biphasic electrical waveform so as to induce analgesia at said site.
Preferably, said two or more locations do not overlie the central nervous system, i.e., brain or spinal cord. More preferably, at least one location is not in the immediate vicinity of the spinal cord, for example is not on the neck, and/or is located more than 10 or 15 cm laterally from the spine and/or on the ventral side of the body. The locations preferably span, i.e., are above and below or on either side of, the area of pain or discomfort, and/or peripheral nerves conducting signals from said area of pain or discomfort. They preferably provide current through an area which includes the area of pain or discomfort, and/or peripheral nerves conducting signals from said area of pain or discomfort. For example, at least one location may be on or in the region of a limb (arm or leg including the hand or foot), the abdomen or the face.
The method of inducing analgesia may be a method of relieving pain or discomfort associated with chronic or acute conditions. For example, it may be a method of relieving pain or discomfort associated with physical injury (including post-operative pain, fracture, bruising, muscle strain and the like), or with chronic or acute diseases or disorders.
Said method may preferably be a method of relieving pain or discomfort associated with inflammatory conditions, particularly rheumatoid arthritis, and other inflammatory arthritic and visceral conditions. The method may also be a method of treating said conditions.
Preferably, the mean pulse width, and more preferably the width of each pulse, is less than 10 μs, more preferably 6 μs or less, 4 μs or less, more preferably 3 μs, 2 μs, 1.5 μs, 1 μs, 0.75 μs or less. It may be preferred that the mean voltage and preferably the voltage of each pulse is at least 100V, preferably at least 150V or 200V.
While all combinations of preferred voltages and pulse widths are specifically included, optionally, in certain embodiments, when the voltage (mean value or voltage of each pulse) is at least 100V, the pulse width (mean value or width of each pulse) is 6 μs or 4 μs or less; when the voltage is at least 150V the pulse width 3 μs or less; and when the voltage is at least 200V the pulse width is 1.5 μs or less.
The pulse frequency may be at least 1200 Hz, more preferably at least 5 kHz, and still more preferably 10 kHz, 20 KHz or above, and/or less than 2 MHz, 1 MHz, 500 KHz, 250 kHz or 100 KHz.
Optionally, Vp2·Pw·Fp is at least 200 and/or less than 1200 or 1800. In some embodiments, the waveform is a HPSP waveform, as described above.
In another aspect, the present invention comprises a method of selecting treatment parameters during the induction of analgesia through electrical signals applied by electrodes to the patient's body, wherein said therapy comprises:
providing an apparatus comprising electrodes for application to the patient's body and a signal generator connectable to said electrodes, wherein the signal generator is arranged to generate a biphasic waveform comprising a successive cycles each containing a forward and reverse pulse,applying the electrodes to two or more locations on the patient's body;
and providing said waveform at a starting voltage and pulse width;
the method of selecting treatment parameters comprising varying the voltage and/or pulse width until the patient experiences a comfortable level of sensation, and selecting the voltage and pulse width at which comfortable sensation is felt.
Preferably, the method comprises varying the pulse voltage, e.g., so that the mean pulse voltage and preferably the voltage of each pulse is varied within the range of 0-500V, preferably 0-250V, 200V or 150V.
The starting pulse width (mean value and preferably also value for each pulse width), may be 10 μs or below, most preferably 4 μs or below. It is preferably varied in the range of 0.01 μs, 0.05 μs or 0.5 μs to 4 μs or 10 μs.
Optionally, the method also comprises providing the waveform at a starting interpulse spacing, and varying the interpulse spacing, e.g., in the range of 0 μs-20 μs, preferably in the range of 0 μs-10 μs. In this embodiment, the starting pulse width (mean value and preferably also value for each pulse width) may be 4 μs or less.
The pulse frequency may be greater than 1200 Hz, more preferably at least 5 kHz, and still more preferably 10 kHz or 20 KHz or above.
In a preferred embodiment, the method comprises a further step of, after selecting the voltage and pulse width at which comfortable sensation is felt, increasing the number of pulses per second Fp such that Fp is at least 200/(Vp2·Pw) but preferably less than 1800/(Vp2·Pw) or 1200/(Vp2·Pw). Preferably, Fp is at least 300/(Vp2·Pw) or 400/(Vp2·Pw).
In some or all of the aspects of the invention described above, it may be preferred each pulse of the biphasic waveform has fast rise and fall, e.g., is substantially rectangular, subject to capacitor droop. It may have an edge rate of 250V/μs or above, more preferably 500V/μs or 1000V/μs or above.
In some or all of these aspects, the biphasic waveform may be a “burst” waveform comprising a train a multiple pulses followed by a quiet period. However, it may be preferred that it is a continuous wave form, in which case it is preferred that the duty cycle (the ratio of “on time” to “off time”) through one complete cycle is preferably be less than 10% or 5%, more preferably less than 2% or 1%, and preferably greater than 0.1%.
It may also be preferred that the amount of electrical charge in the forward and reverse pulse is equal. This gives a mean current of zero, and helps to minimise ionic transport. Conveniently, this can be achieved by having a forward and reverse pulse of equal voltage and pulse width. If the amplitude (voltage) or pulse width is not equal for the forward and reverse pulse, then the mean value for the two pulses is calculated. In the case where it is desired the amplitude or pulse width of the second pulse is not the same as the first pulse, then the parameters of the second pulse are preferably adjusted so the mean value of the voltage applied to the patient is zero.
It may further be preferred that the apparatus for providing analgesia in a patient comprises a single signal generator arranged to produce one biphasic waveform. Similarly, it is preferred that some or all of the methods comprise the provision of a single biphasic waveform from a single signal generator. If more than one waveform is provided by the apparatus/method, then it is preferred that these waveforms are of the same cycle frequency, or that one is an integer multiple of the other to reduce interference effects.
A difficulty with treatment methods which involve imparting relatively high power to the patient is that safety mechanisms must be put in place which prevent a dangerous level of charge from being applied in the event of malfunction. This is also a concern in an apparatus in which variable frequency, pulse width and voltage can be applied.
There are two international safety standards of particular relevance, these are IEC 60601-2-10, “Particular requirements for the safety of nerve and muscle stimulators” and the US standard AAMI NS4-1985 (Transcutaneous Electrical Nerve Stimulation).
Key safety requirements of 60601-2-10 are:                Maximum limits on output current (rms) are 80 mA at DC, 50 mA at 400 Hz, 80 mA at 1500 Hz and 100 mA above 1500 Hz (with a 500 ohm resistive load).        The maximum pulse energy should not exceed 300 mJ.        The peak output voltage should not exceed 500V.        
AAMI NS4 is being revised and its American National Standard status has been withdrawn because it is more than 10 years old. It however remains an AAMI (Association for the Advancement of Medical Instrumentation) standard and is the most directly relevant published document for the design of TENS devices. The key requirements of NS4 are:                Resistive loads of 200 Ω, 500Ω and 1 kΩ are defined as the test loads. 500Ω resistive is considered as the reference waveform for safety purposes.        The minimum output for efficacy (with the controls at maximum) is either 7 μC per pulse or a complex waveform whose average stimulating component amplitude is at least 0.5 mA into a load of 500 Ω.        The maximum charge per pulse should under no circumstances exceed 75 μC into a 500Ω load.        Maximum average current shall not exceed 10 mA, the limit for DC currents to reduce burns due to ionic transport.        
In GB 2 290 033, it is suggested that a capacitor could be placed in series with one of the electrodes to isolate the patient from the possibility of direct current stimulation. However, such an arrangement is not suitable for producing square wave shaped pulses.
In a further aspect, the present invention provides an apparatus for producing analgesia in a patient through electrical signals applied by electrodes to the patient's body, the apparatus comprising electrodes for application to the patient's body and a signal generator which is connectable to the electrodes, wherein the signal generator is arranged to generate a biphasic waveform comprising successive cycles each containing a positive and negative pulse, and comprises:
a converter for producing a desired voltage from a power supply;
a first capacitor which is in electrical connection with said converter and which is arranged to provide the positive pulse to one of said electrodes;
a second capacitor which is in electrical connection with said converter and which is arranged to provide the negative pulse to one of said electrodes;
wherein said first and second capacitors are respectively connected to an output by a corresponding pathway, the pathways including respective switches, and wherein the signal generator includes a controller arranged to control the operation of the switches to cause alternate discharge of the first and second capacitors through the corresponding pathway to generate said positive and negative pulses.
This apparatus may thus be operable so that it cannot generate a sustained harmful average current, particularly where the converter produces a desired voltage but is limited in current output, so that it cannot generate a dangerous current during the pulse time either by itself or in combination with the capacitors, nor deliver a pulse of more than the safety value in the even of either software failure or single component failure.
An advantage of this apparatus is that a key safety measure limiting the amount of charge which would be applied to the patient in the event of malfunction is present in the hardware.
The inventors have realised that in order to limit the current which can be supplied in the event of malfunction to an acceptable level, it is desirable that sum total of the charge transferred in the positive and negative cycles plus the current which can be supplied by the converter over the pulse period should not exceed a dangerous level. Preferably, it does not exceed a maximum of 75 μC, e.g., even under fault conditions.
As a result of these considerations, there is a limit on the rate that charge can be delivered from the converter and/or on the amount of charge which can be stored in the capacitors. As a result, there may be a significant droop in voltage over the pulse period, particularly for pulses of longer duration.
In the present apparatus, the wave is produced by discharging two independent capacitors fed from a common converter, one providing the positive pulse and one providing the negative pulse. This produces a wave which is substantially symmetrical in nature, since any voltage drop over the course of the capacitor discharge affects the positive and negative pulse to the same extent.
The converter is preferably adapted to produce the desired voltage from a battery, though it may also be adapted to produce the desired voltage from the mains supply as an additional or alternative source. The apparatus may optionally include a suitable battery, e.g., a rechargeable battery.
In a preferred embodiment, the signal generator produces an output which has a fast rise and fall phase, e.g., is substantially rectangular.
The output may have a pulse current (i.e., a peak pulse current) of greater than 1 A, 1.5 A or 2 A or 3 A. It may optionally be preferred that the output Vp2·Pw·Fp>200. In some embodiments, the output will be a HPSP wave, as described above.
It is preferred that the capacitance of the capacitor decreases with voltage. This improves the ability of the device to be with a wide voltage range, storing only a safe level of charge at a high voltage but also storing enough charge at a low voltage to deliver effective stimulation with longer pulses, which are necessary at lower voltages. Ceramic type capacitors are particularly preferred.
In a preferred embodiment, when no output from the capacitor is desired, i.e. during the pulse off time, switches in the pathway connecting each capacitor to the output are turned off and an additional switch or switches are operated to short the patient outputs together either directly or via device OV. Preferably, the apparatus includes a control to control the operation of said switches. This helps to provide a rapid return of the trailing edge of the pulse to zero. Preferably, the edge rate is greater than 250 V/μs, more preferably greater than 500V/μs or 1000V/μs.
In preferred embodiments, further control and safety systems are provided. For example, pulse width may be controlled and/or limited by one, two or more independent systems. For example, pulse width can be limited by a logic circuit and/or by output transistors which cannot remain in the “on” state for more than a fixed period without edge transitions on the gate drives. The latter also protects against a microprocessor failure since the microprocessor may be expected to fail with its outputs in a frozen state.
By careful selection of the capacitor rating and the use of pulse “on time” limiting controls (such as circuitry in the switch drive logic, and level translation circuitry) the apparatus can be designed with a wide range of pulse and output voltage where the therapeutic pulse charge does not exceed 25 μC per pulse under normal operating conditions, and 75 μC per pulse under single or double fault conditions.
The signal generator may also include one, two or more independent means of monitoring the signal, for example monitoring the current and/or voltage produced by the apparatus. These may include means for measuring the output current from the converter (wherein the measured current may be fed back into hardware circuitry in the converter to provide either a current limit or a current control loop and/or fed into a microprocessor for monitoring processes), means for measuring the current from one or both capacitors, and/or a means for measuring the voltage and current applied to the patient.
Preferably, said first and second capacitors are respectively connected by a corresponding pathway to an output path to the patient. Means for monitoring this signal may preferably be located in the output path. Alternatively, if electronically more convenient, it may be located in the in the return pathway from the output since this is at device OV potential and therefore does not require translation of the signal from the output sensor.
Preferably, the device includes a safety device which operates to discharge the capacitors to device OV in the event that the voltage in either pathway and/or the output current exceeds a predetermined limit, e.g., as detected by monitoring circuits implemented in hardware. Most preferably, this device is a Silicon Controlled Rectifier (SCR). In preferred embodiments, the device should also be operable by a microprocessor in the event of an error or shutdown identified by the microprocessor.
Preferably, the apparatus comprises at least two independent circuits for monitoring the voltage and/or current produced by the apparatus and also comprises means for comparing the measured values, thus enabling an error in either circuit to be detected, and optionally causing shutdown of the device.
Means for monitoring and/or comparing the signal and/or controlling discharge of a pathway should preferably be implemented in hardware and conveniently may also be implemented using a microprocessor as backup.
While aspects of the invention have been discussed independently, they may also be used together in any combination.
In the above aspects of the invention, the electrodes of the device may be either surface electrodes or implanted electrodes. References to the application of an electrode to a location on the patient's body are to be construed accordingly to include electrode implantation. Normally, implanted electrodes are covered with insulating material except at their tip, but this is not essential.